The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the ...role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.
A wide variety of industrial applications require materials with high strength and ductility. Unfortunately, the strategies for increasing material strength, such as processing to create line defects ...(dislocations), tend to decrease ductility. We developed a strategy to circumvent this in inexpensive, medium manganese steel. Cold rolling followed by low-temperature tempering developed steel with metastable austenite grains embedded in a highly dislocated martensite matrix. This deformed and partitioned (D and P) process produced dislocation hardening but retained high ductility, both through the glide of intensive mobile dislocations and by allowing us to control martensitic transformation. The D and P strategy should apply to any other alloy with deformation-induced martensitic transformation and provides a pathway for the development of high-strength, high-ductility materials.
We report on the observation of new properties of secondary cosmic rays Li, Be, and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV with a total of 5.4×10^{6} nuclei ...collected by AMS during the first five years of operation aboard the International Space Station. The Li and B fluxes have an identical rigidity dependence above 7 GV and all three fluxes have an identical rigidity dependence above 30 GV with the Li/Be flux ratio of 2.0±0.1. The three fluxes deviate from a single power law above 200 GV in an identical way. This behavior of secondary cosmic rays has also been observed in the AMS measurement of primary cosmic rays He, C, and O but the rigidity dependences of primary cosmic rays and of secondary cosmic rays are distinctly different. In particular, above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays.
Lignin is a key component in the biomass with a complex polymeric structure of the phenyl-C3 alkyl units. The kraft lignin from the wood pulping process is tested in TG-FTIR and Py-GC-MS. The samples ...are pyrolyzed in TGA coupled with FTIR from 30 to 900°C at the heating rate of 20 and 40K/min. The evolution of phenolic compounds in the initial pyrolysis stage of lignin is determined by FTIR, while the second stage is mainly attributed to the production of the low molecular weight species. A bench-scale fast pyrolysis unit is employed to investigate the effect of temperature on the product yield and composition. It is found that the guaiacol-type and syringol-type compounds as the primary products of lignin pyrolysis are predominant in bio-oil, acting as the significant precursors for the formation of the derivatives such as the phenol-, cresol- and catechol-types. A series of free-radical chain-reactions, concerning the cracking of different side-chain structures and the methoxy groups on aromatic ring, are proposed to demonstrate the formation pathways for the typical compounds in bio-oil by closely relating lignin structure to the pyrolytic mechanisms. The methoxy group (–OCH3) is suggested to work as an important source for the formation of the small volatile species (CO, CO2 and CH4) through the relevant free radical coupling reactions.
Deformation twinning plays a vital role in accommodating plastic deformation of hexagonal-close-packed (hcp) metals, but its mechanisms are still unsettled under high strain rate shock compression. ...Here we investigate deformation twinning in shock-compressed Mg as a typical hcp metal with in situ, ultrafast synchrotron x-ray diffraction. Extension twinning occurs upon shock compression along ⟨112over ¯0⟩ and ⟨101over ¯0⟩, but only upon release for loading along ⟨0001⟩. Such deformation mechanisms are a result of the polarity of deformation twinning, which depends on directionality and relative magnitude of resolved shear stress and may be common for Mg and its alloys in a wide range of strain rates.
Abstract Parkinson's disease (PD) is a progressive neurological disorder that is often associated with various gastrointestinal (GI) symptoms. The link between the alteration of dopaminergic system ...and the symptoms of the GI tract in PD is complicated. To determine the changes in the dopaminergic system in the GI tract in PD, two kinds of rodent PD models were used in the present study. One was 6-hydroxydopamine (6-OHDA) -treated rats in which 6-OHDA was microinjected in the bilateral substantia nigra (SN). The other was 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -treated mice in which MPTP was injected intraperitoneally. Immunofluorescence, reverse transcription (RT)-real time polymerase chain reaction (PCR) and Western blot were used to evaluate and compare the levels of mRNA and protein expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the GI tract between normal and rodent PD models, as well as between 6-OHDA-treated rats and MPTP-treated mice. The results indicated that TH- and DAT-positive cells were widely distributed in the GI tract. There were significant differences in TH and DAT expression in the GI tract between normal and PD models, as well as between 6-OHDA-treated rats and MPTP-treated mice. The protein levels of TH and DAT in the GI tract were significantly increased in 6-OHDA-treated rats, but the protein level of TH was significantly decreased in MPTP-treated mice. In addition, there was visible atrophy of gastric epithelial parietal cells in MPTP-treated mice, although the protein level of DAT was not significantly changed. The different alterations of dopaminergic system in the GI tract of the two kinds of PD models might underline the differences in GI symptoms in PD patients and might be correlated with the disease severity and disease process affecting the GI tract.
Long non coding RNA (LncRNA) urothelial carcinoma-associated 1 (UCA1) is an oncogene in breast cancer. However, the detailed mechanism has not been fully revealed. This study explored whether UCA1 ...can directly interact with miR-143, a tumor suppressor in breast cancer and whether the UCA1-miR-143 axis is involved in regulation of cancer cell growth and apoptosis.
miRNA microarray was performed to identify the most dysregulated miRNAs between tumor and adjacent normal tissues of breast cancer. QRT-PCR analysis was performed to assess the expression of UCA1 and miR-143. The binding between UCA1 and miR-143 was verified using dual luciferase and RNA binding protein immunoprecipitation (RIP) assay. MTT assay and flow cytometry analysis were performed to study the role of UCA1-miR-143 axis in cell proliferation, cell cycle and apoptosis.
UC1 was significantly upregulated, while miR-143 was significantly downregulated in the tumor tissues than in the adjacent normal tissues. There are direct interactions between miR-143 and the miRNA recognition sites of UCA1. UCA1 is present in Ago2-containing RNA-induced silencing complex (RISC), through association with miR-143. Through downregulating miR-143, UCA1 can modulate breast cancer cell growth and apoptosis.
UCA1 can directly interact with miR-143, lower its expression and affect its downstream regulation. Therefore, the UCA1-miR-143 axis constitutes a part of the oncogenic role of UCA1 in breast cancer.
Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in ...behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1
knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1
mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1β (IL-1β) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1β in both WT and Caspase-1
mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1β axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.
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